BRPI0612777A2 - derivados de heteroariletenila, sua fabricação e uso como agentes farmacêuticos - Google Patents
derivados de heteroariletenila, sua fabricação e uso como agentes farmacêuticos Download PDFInfo
- Publication number
- BRPI0612777A2 BRPI0612777A2 BRPI0612777-0A BRPI0612777A BRPI0612777A2 BR PI0612777 A2 BRPI0612777 A2 BR PI0612777A2 BR PI0612777 A BRPI0612777 A BR PI0612777A BR PI0612777 A2 BRPI0612777 A2 BR PI0612777A2
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- BR
- Brazil
- Prior art keywords
- formula
- acid
- sodium salt
- benzoylamide
- pyridin
- Prior art date
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- 238000004519 manufacturing process Methods 0.000 title claims abstract description 20
- 239000008177 pharmaceutical agent Substances 0.000 title abstract description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 157
- 150000003839 salts Chemical class 0.000 claims abstract description 25
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 20
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 11
- 238000002360 preparation method Methods 0.000 claims abstract description 8
- 201000011510 cancer Diseases 0.000 claims abstract description 7
- -1 chloro, bromo, methyl Chemical group 0.000 claims description 141
- 239000002253 acid Substances 0.000 claims description 93
- 125000000217 alkyl group Chemical group 0.000 claims description 57
- 159000000000 sodium salts Chemical class 0.000 claims description 42
- 238000000034 method Methods 0.000 claims description 41
- 125000003545 alkoxy group Chemical group 0.000 claims description 40
- 238000006243 chemical reaction Methods 0.000 claims description 31
- 229910052736 halogen Inorganic materials 0.000 claims description 26
- 150000002367 halogens Chemical class 0.000 claims description 26
- 125000004076 pyridyl group Chemical group 0.000 claims description 23
- 125000001544 thienyl group Chemical group 0.000 claims description 23
- 239000000460 chlorine Substances 0.000 claims description 21
- 229910052801 chlorine Inorganic materials 0.000 claims description 21
- XXFUNTSOBHSMBU-UHFFFAOYSA-N 2,4-dichlorobenzamide Chemical compound NC(=O)C1=CC=C(Cl)C=C1Cl XXFUNTSOBHSMBU-UHFFFAOYSA-N 0.000 claims description 17
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 16
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 16
- 229910052731 fluorine Inorganic materials 0.000 claims description 16
- 239000011737 fluorine Substances 0.000 claims description 16
- 125000002950 monocyclic group Chemical group 0.000 claims description 15
- 239000011734 sodium Substances 0.000 claims description 15
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 15
- 150000003456 sulfonamides Chemical class 0.000 claims description 14
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 12
- 229910052794 bromium Chemical group 0.000 claims description 12
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 230000008569 process Effects 0.000 claims description 11
- 229940124530 sulfonamide Drugs 0.000 claims description 11
- 125000001153 fluoro group Chemical group F* 0.000 claims description 10
- 229910052708 sodium Inorganic materials 0.000 claims description 10
- 125000001246 bromo group Chemical group Br* 0.000 claims description 9
- 239000003795 chemical substances by application Substances 0.000 claims description 9
- UFXIIQGMMJQZPG-UHFFFAOYSA-N 2,4-bis(trifluoromethyl)benzamide Chemical compound NC(=O)C1=CC=C(C(F)(F)F)C=C1C(F)(F)F UFXIIQGMMJQZPG-UHFFFAOYSA-N 0.000 claims description 8
- 239000005711 Benzoic acid Substances 0.000 claims description 8
- 235000010233 benzoic acid Nutrition 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 7
- OXAZYPDRGPSAEZ-UHFFFAOYSA-N 4-chloro-2-methoxybenzamide Chemical compound COC1=CC(Cl)=CC=C1C(N)=O OXAZYPDRGPSAEZ-UHFFFAOYSA-N 0.000 claims description 6
- HRJKVZCCWLPFMF-UHFFFAOYSA-N 4-fluoro-2-(trifluoromethyl)benzamide Chemical compound NC(=O)C1=CC=C(F)C=C1C(F)(F)F HRJKVZCCWLPFMF-UHFFFAOYSA-N 0.000 claims description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
- OXVDLPSKMYAHFN-SNAWJCMRSA-N COC1=CC=C(\C=C\S(O)(=O)=O)C=N1 Chemical compound COC1=CC=C(\C=C\S(O)(=O)=O)C=N1 OXVDLPSKMYAHFN-SNAWJCMRSA-N 0.000 claims description 6
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 6
- 238000003776 cleavage reaction Methods 0.000 claims description 6
- 230000007017 scission Effects 0.000 claims description 6
- GWLFXUUYBRACSN-UHFFFAOYSA-N 2,4-dimethylbenzamide Chemical compound CC1=CC=C(C(N)=O)C(C)=C1 GWLFXUUYBRACSN-UHFFFAOYSA-N 0.000 claims description 5
- IWODMEGZVDWKPK-UHFFFAOYSA-N 2-bromo-4-fluorobenzamide Chemical compound NC(=O)C1=CC=C(F)C=C1Br IWODMEGZVDWKPK-UHFFFAOYSA-N 0.000 claims description 5
- 230000001028 anti-proliverative effect Effects 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 230000002401 inhibitory effect Effects 0.000 claims description 4
- 229910052740 iodine Inorganic materials 0.000 claims description 4
- BLPQKUHSUYTZJG-UHFFFAOYSA-M sodium (2,4-dichlorobenzoyl)azanide Chemical compound [Na+].[NH-]C(=O)c1ccc(Cl)cc1Cl BLPQKUHSUYTZJG-UHFFFAOYSA-M 0.000 claims description 4
- 230000004614 tumor growth Effects 0.000 claims description 4
- DEFPPCHBZBKDID-HWKANZROSA-N (e)-2-thiophen-2-ylethenesulfonic acid Chemical compound OS(=O)(=O)\C=C\C1=CC=CS1 DEFPPCHBZBKDID-HWKANZROSA-N 0.000 claims description 3
- 206010025323 Lymphomas Diseases 0.000 claims description 3
- 206010029260 Neuroblastoma Diseases 0.000 claims description 3
- 210000000481 breast Anatomy 0.000 claims description 3
- 230000002496 gastric effect Effects 0.000 claims description 3
- 210000004072 lung Anatomy 0.000 claims description 3
- 201000001441 melanoma Diseases 0.000 claims description 3
- IAERXWWSCMVLEP-UHFFFAOYSA-N n-(2,4,4-trimethylpentan-2-yl)ethenesulfonamide Chemical compound CC(C)(C)CC(C)(C)NS(=O)(=O)C=C IAERXWWSCMVLEP-UHFFFAOYSA-N 0.000 claims description 3
- YDGWZTQORFEMST-UHFFFAOYSA-N n-(2,4,4-trimethylpentan-2-yl)methanesulfonamide Chemical compound CC(C)(C)CC(C)(C)NS(C)(=O)=O YDGWZTQORFEMST-UHFFFAOYSA-N 0.000 claims description 3
- 230000002611 ovarian Effects 0.000 claims description 3
- 210000002307 prostate Anatomy 0.000 claims description 3
- PEXCDDFWOIUBNR-UHFFFAOYSA-N 4-bromo-2-methylbenzamide Chemical compound CC1=CC(Br)=CC=C1C(N)=O PEXCDDFWOIUBNR-UHFFFAOYSA-N 0.000 claims description 2
- VRVMBIZATLJJFO-UHFFFAOYSA-N 4-chloro-2-methylbenzamide Chemical compound CC1=CC(Cl)=CC=C1C(N)=O VRVMBIZATLJJFO-UHFFFAOYSA-N 0.000 claims description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims description 2
- 239000011630 iodine Substances 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
- XIQZTMMWBKPFSE-UHFFFAOYSA-N 2-chloro-4-fluorobenzamide Chemical compound NC(=O)C1=CC=C(F)C=C1Cl XIQZTMMWBKPFSE-UHFFFAOYSA-N 0.000 claims 3
- XRYKFEFVHWQOKB-IPZCTEOASA-N (E)-2-(1-benzothiophen-3-yl)ethenesulfonic acid 2,4-bis(trifluoromethyl)benzamide Chemical compound C1=CC=C2C(/C=C/S(=O)(=O)O)=CSC2=C1.NC(=O)C1=CC=C(C(F)(F)F)C=C1C(F)(F)F XRYKFEFVHWQOKB-IPZCTEOASA-N 0.000 claims 1
- OPGQXJZGMYQQFW-AATRIKPKSA-N (e)-2-(1-benzothiophen-3-yl)ethenesulfonic acid Chemical compound C1=CC=C2C(/C=C/S(=O)(=O)O)=CSC2=C1 OPGQXJZGMYQQFW-AATRIKPKSA-N 0.000 claims 1
- JBRWQVKSMBKLIT-GQCTYLIASA-N (e)-2-pyridin-2-ylethenesulfonic acid Chemical compound OS(=O)(=O)\C=C\C1=CC=CC=N1 JBRWQVKSMBKLIT-GQCTYLIASA-N 0.000 claims 1
- MTKFBCYEWUMSAQ-UHFFFAOYSA-N 2,3-bis(trifluoromethyl)benzamide Chemical compound NC(=O)C1=CC=CC(C(F)(F)F)=C1C(F)(F)F MTKFBCYEWUMSAQ-UHFFFAOYSA-N 0.000 claims 1
- JNOIFICNZNJWKZ-UHFFFAOYSA-N 2-(3-bromothiophen-2-yl)ethenesulfonic acid Chemical compound OS(=O)(=O)C=CC=1SC=CC=1Br JNOIFICNZNJWKZ-UHFFFAOYSA-N 0.000 claims 1
- VKLWBHPTGFYMDC-UHFFFAOYSA-N 2-(6-methylpyridin-2-yl)ethenesulfonic acid Chemical compound CC1=CC=CC(C=CS(O)(=O)=O)=N1 VKLWBHPTGFYMDC-UHFFFAOYSA-N 0.000 claims 1
- ORFWVGHYCXGUHS-UHFFFAOYSA-N 4-bromo-2-chlorobenzamide Chemical compound NC(=O)C1=CC=C(Br)C=C1Cl ORFWVGHYCXGUHS-UHFFFAOYSA-N 0.000 claims 1
- IRNSIGSVOVMTKF-GWDXERMASA-N 4-bromo-2-methylbenzamide (E)-2-pyridin-3-ylethenesulfonic acid Chemical compound CC1=CC(Br)=CC=C1C(N)=O.OS(=O)(=O)\C=C\C1=CC=CN=C1 IRNSIGSVOVMTKF-GWDXERMASA-N 0.000 claims 1
- COLYSKPQWVYLGX-SOFGYWHQSA-N 4-chloro-2-methoxy-n-[(e)-2-pyridin-3-ylethenyl]sulfonylbenzamide Chemical compound COC1=CC(Cl)=CC=C1C(=O)NS(=O)(=O)\C=C\C1=CC=CN=C1 COLYSKPQWVYLGX-SOFGYWHQSA-N 0.000 claims 1
- 206010005003 Bladder cancer Diseases 0.000 claims 1
- LLHTXKOWNXRNOW-UHFFFAOYSA-N C=C(C1=CSC=C1)S(=O)(=O)O Chemical compound C=C(C1=CSC=C1)S(=O)(=O)O LLHTXKOWNXRNOW-UHFFFAOYSA-N 0.000 claims 1
- 208000008839 Kidney Neoplasms Diseases 0.000 claims 1
- FJTCBYGKQPSMGD-DUXPYHPUSA-N OS(=O)(=O)\C=C\C=1C=CSC=1 Chemical compound OS(=O)(=O)\C=C\C=1C=CSC=1 FJTCBYGKQPSMGD-DUXPYHPUSA-N 0.000 claims 1
- 206010038389 Renal cancer Diseases 0.000 claims 1
- BVJOCRUVBGLTEX-UHFFFAOYSA-N S1C=C(C=C1)[Na] Chemical class S1C=C(C=C1)[Na] BVJOCRUVBGLTEX-UHFFFAOYSA-N 0.000 claims 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims 1
- QDPMLKBAQOZXEF-UHFFFAOYSA-N ethanesulfonic acid;sodium Chemical class [Na].CCS(O)(=O)=O QDPMLKBAQOZXEF-UHFFFAOYSA-N 0.000 claims 1
- 201000010982 kidney cancer Diseases 0.000 claims 1
- 208000032839 leukemia Diseases 0.000 claims 1
- VMDCXYHZENUPQE-BQYQJAHWSA-N n-[(e)-2-(1-benzothiophen-3-yl)ethenyl]sulfonyl-2-bromo-4-fluorobenzamide Chemical compound BrC1=CC(F)=CC=C1C(=O)NS(=O)(=O)\C=C\C1=CSC2=CC=CC=C12 VMDCXYHZENUPQE-BQYQJAHWSA-N 0.000 claims 1
- YNICOJSWEAJZJS-VOTSOKGWSA-N n-[(e)-2-(6-methoxypyridin-3-yl)ethenyl]sulfonyl-2,4-bis(trifluoromethyl)benzamide Chemical compound C1=NC(OC)=CC=C1\C=C\S(=O)(=O)NC(=O)C1=CC=C(C(F)(F)F)C=C1C(F)(F)F YNICOJSWEAJZJS-VOTSOKGWSA-N 0.000 claims 1
- NCCHARWOCKOHIH-UHFFFAOYSA-N n-methylbenzamide Chemical compound CNC(=O)C1=CC=CC=C1 NCCHARWOCKOHIH-UHFFFAOYSA-N 0.000 claims 1
- AKKCPZWNURMNNR-UHFFFAOYSA-M sodium (4-chloro-2-methoxybenzoyl)azanide Chemical compound [Na+].COc1cc(Cl)ccc1C([NH-])=O AKKCPZWNURMNNR-UHFFFAOYSA-M 0.000 claims 1
- 201000005112 urinary bladder cancer Diseases 0.000 claims 1
- 230000006806 disease prevention Effects 0.000 abstract description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 99
- 239000000203 mixture Substances 0.000 description 56
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 36
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 36
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 28
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 28
- 239000000243 solution Substances 0.000 description 26
- 239000002904 solvent Substances 0.000 description 23
- 125000001072 heteroaryl group Chemical group 0.000 description 21
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 19
- 210000004027 cell Anatomy 0.000 description 17
- 238000005160 1H NMR spectroscopy Methods 0.000 description 16
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 16
- 239000007787 solid Substances 0.000 description 16
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 15
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
- 230000004913 activation Effects 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 10
- QIJIUJYANDSEKG-UHFFFAOYSA-N 2,4,4-trimethylpentan-2-amine Chemical compound CC(C)(C)CC(C)(C)N QIJIUJYANDSEKG-UHFFFAOYSA-N 0.000 description 10
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 10
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
- 125000004432 carbon atom Chemical group C* 0.000 description 10
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 10
- 239000003153 chemical reaction reagent Substances 0.000 description 9
- 125000000842 isoxazolyl group Chemical group 0.000 description 9
- 239000003921 oil Substances 0.000 description 9
- 235000019198 oils Nutrition 0.000 description 9
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
- 125000005842 heteroatom Chemical group 0.000 description 8
- 229910052760 oxygen Inorganic materials 0.000 description 8
- 125000000714 pyrimidinyl group Chemical group 0.000 description 8
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 7
- 150000001408 amides Chemical class 0.000 description 7
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 7
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 7
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 7
- 125000000335 thiazolyl group Chemical group 0.000 description 7
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- 125000003118 aryl group Chemical group 0.000 description 6
- 125000002619 bicyclic group Chemical group 0.000 description 6
- 238000005660 chlorination reaction Methods 0.000 description 6
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- 239000012312 sodium hydride Substances 0.000 description 6
- 229910000104 sodium hydride Inorganic materials 0.000 description 6
- 229910052717 sulfur Inorganic materials 0.000 description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 5
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 230000007246 mechanism Effects 0.000 description 5
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 5
- 125000006413 ring segment Chemical group 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- SJUKJZSTBBSGHF-UHFFFAOYSA-N (2,4-dichlorophenyl)methanamine Chemical compound NCC1=CC=C(Cl)C=C1Cl SJUKJZSTBBSGHF-UHFFFAOYSA-N 0.000 description 4
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 4
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 4
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 4
- OKEFBVALFLRAFV-UHFFFAOYSA-N 4-chloro-2-methoxybenzoyl chloride Chemical compound COC1=CC(Cl)=CC=C1C(Cl)=O OKEFBVALFLRAFV-UHFFFAOYSA-N 0.000 description 4
- HJCMDXDYPOUFDY-WHFBIAKZSA-N Ala-Gln Chemical compound C[C@H](N)C(=O)N[C@H](C(O)=O)CCC(N)=O HJCMDXDYPOUFDY-WHFBIAKZSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 108060001084 Luciferase Proteins 0.000 description 4
- 239000005089 Luciferase Substances 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- 230000010933 acylation Effects 0.000 description 4
- 238000005917 acylation reaction Methods 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 230000008030 elimination Effects 0.000 description 4
- 238000003379 elimination reaction Methods 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 239000007903 gelatin capsule Substances 0.000 description 4
- 125000002883 imidazolyl group Chemical group 0.000 description 4
- 125000001041 indolyl group Chemical group 0.000 description 4
- 238000002953 preparative HPLC Methods 0.000 description 4
- 125000003226 pyrazolyl group Chemical group 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
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- 235000021355 Stearic acid Nutrition 0.000 description 1
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- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
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- 239000008101 lactose Substances 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 1
- WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 description 1
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- 238000000691 measurement method Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
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- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
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- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
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- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical class CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
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- PLQIOFZPHAZJAM-UHFFFAOYSA-N oxo(phenyl)methanesulfonamide Chemical class NS(=O)(=O)C(=O)C1=CC=CC=C1 PLQIOFZPHAZJAM-UHFFFAOYSA-N 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
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- 239000012071 phase Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
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- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
- QJZUKDFHGGYHMC-UHFFFAOYSA-N pyridine-3-carbaldehyde Chemical compound O=CC1=CC=CN=C1 QJZUKDFHGGYHMC-UHFFFAOYSA-N 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
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- 230000002829 reductive effect Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
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- 229960004889 salicylic acid Drugs 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000003333 secondary alcohols Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- NZIOGURHMIGHST-UHFFFAOYSA-N sodium sulfoazanide Chemical class [Na+].[NH-]S(O)(=O)=O NZIOGURHMIGHST-UHFFFAOYSA-N 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- NOJNFULGOQGBKB-UHFFFAOYSA-M sodium;3-[3-tert-butylsulfanyl-1-[[4-(6-ethoxypyridin-3-yl)phenyl]methyl]-5-[(5-methylpyridin-2-yl)methoxy]indol-2-yl]-2,2-dimethylpropanoate Chemical compound [Na+].C1=NC(OCC)=CC=C1C(C=C1)=CC=C1CN1C2=CC=C(OCC=3N=CC(C)=CC=3)C=C2C(SC(C)(C)C)=C1CC(C)(C)C([O-])=O NOJNFULGOQGBKB-UHFFFAOYSA-M 0.000 description 1
- 238000009331 sowing Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
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- 239000006188 syrup Substances 0.000 description 1
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- 239000007916 tablet composition Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
- 230000004565 tumor cell growth Effects 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/50—Compounds containing any of the groups, X being a hetero atom, Y being any atom
- C07C311/51—Y being a hydrogen or a carbon atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/18—Sulfonamides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
- A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
- C07C311/11—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic unsaturated carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/59—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with at least one of the bonds being to sulfur
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Pyridine Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP05014789.1 | 2005-07-07 | ||
| EP05014789 | 2005-07-07 | ||
| EP06001008 | 2006-06-18 | ||
| EP06001008.9 | 2006-06-18 | ||
| PCT/EP2006/006523 WO2007006459A1 (en) | 2005-07-07 | 2006-07-05 | Heteroarylethenyl derivatives, their manufacture and use as pharmaceutical agents |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BRPI0612777A2 true BRPI0612777A2 (pt) | 2010-11-30 |
Family
ID=37198975
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BRPI0612777-0A BRPI0612777A2 (pt) | 2005-07-07 | 2006-07-05 | derivados de heteroariletenila, sua fabricação e uso como agentes farmacêuticos |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US7208506B2 (de) |
| EP (1) | EP1904471B1 (de) |
| JP (1) | JP2009501158A (de) |
| KR (1) | KR20080015045A (de) |
| CN (1) | CN101208325A (de) |
| AR (1) | AR054532A1 (de) |
| AT (1) | ATE446291T1 (de) |
| AU (1) | AU2006269015A1 (de) |
| BR (1) | BRPI0612777A2 (de) |
| CA (1) | CA2612752A1 (de) |
| DE (1) | DE602006009939D1 (de) |
| ES (1) | ES2332421T3 (de) |
| IL (1) | IL187419A0 (de) |
| MX (1) | MX2007015035A (de) |
| WO (1) | WO2007006459A1 (de) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2010526844A (ja) * | 2007-05-16 | 2010-08-05 | エフ．ホフマン−ラ ロシュ アーゲー | アリールピリジルスルホンアミド誘導体、それらの製造法及び医薬剤としての使用 |
| CN112479851B (zh) * | 2020-11-16 | 2022-11-15 | 中国医学科学院药用植物研究所 | 山椒子烯酮衍生物、其制备方法和应用 |
| WO2026006805A1 (en) * | 2024-06-28 | 2026-01-02 | Amgen Inc. | 6-membered core compounds as modulators of werner syndrome recq dna helicase and uses thereof |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4206142A (en) * | 1973-06-11 | 1980-06-03 | Mead Johnson & Company | Styrylamidine process |
| AU745081B2 (en) | 1997-06-27 | 2002-03-14 | Fujisawa Pharmaceutical Co., Ltd. | Sulfonamide compounds and medicinal use thereof |
| US6410584B1 (en) * | 1998-01-14 | 2002-06-25 | Cell Pathways, Inc. | Method for inhibiting neoplastic cells with indole derivatives |
| US20030105144A1 (en) * | 2001-04-17 | 2003-06-05 | Ping Gao | Stabilized oral pharmaceutical composition |
| US7183320B2 (en) | 2001-06-06 | 2007-02-27 | Eli Lilly And Company | Benzoylsulfonamides and sulfonylbenzamidines for use as antitumour agents |
| TWI281916B (en) | 2001-10-25 | 2007-06-01 | Lilly Co Eli | Antitumor compounds and methods |
| DE60316984T2 (de) | 2002-11-22 | 2008-07-17 | Eli Lilly And Co., Indianapolis | Benzoylsulfonamide als antitumor-mittel |
-
2006
- 2006-06-29 US US11/477,641 patent/US7208506B2/en not_active Expired - Fee Related
- 2006-07-05 JP JP2008519852A patent/JP2009501158A/ja active Pending
- 2006-07-05 CN CNA200680023051XA patent/CN101208325A/zh active Pending
- 2006-07-05 EP EP06776122A patent/EP1904471B1/de not_active Not-in-force
- 2006-07-05 MX MX2007015035A patent/MX2007015035A/es active IP Right Grant
- 2006-07-05 WO PCT/EP2006/006523 patent/WO2007006459A1/en not_active Ceased
- 2006-07-05 DE DE602006009939T patent/DE602006009939D1/de active Active
- 2006-07-05 AR ARP060102895A patent/AR054532A1/es not_active Application Discontinuation
- 2006-07-05 AT AT06776122T patent/ATE446291T1/de not_active IP Right Cessation
- 2006-07-05 KR KR1020087000258A patent/KR20080015045A/ko not_active Ceased
- 2006-07-05 CA CA002612752A patent/CA2612752A1/en not_active Abandoned
- 2006-07-05 BR BRPI0612777-0A patent/BRPI0612777A2/pt not_active IP Right Cessation
- 2006-07-05 ES ES06776122T patent/ES2332421T3/es active Active
- 2006-07-05 AU AU2006269015A patent/AU2006269015A1/en not_active Abandoned
-
2007
- 2007-11-15 IL IL187419A patent/IL187419A0/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| MX2007015035A (es) | 2008-01-28 |
| ES2332421T3 (es) | 2010-02-04 |
| CN101208325A (zh) | 2008-06-25 |
| KR20080015045A (ko) | 2008-02-15 |
| ATE446291T1 (de) | 2009-11-15 |
| CA2612752A1 (en) | 2007-01-18 |
| WO2007006459A1 (en) | 2007-01-18 |
| US20070010564A1 (en) | 2007-01-11 |
| US7208506B2 (en) | 2007-04-24 |
| AR054532A1 (es) | 2007-06-27 |
| EP1904471B1 (de) | 2009-10-21 |
| DE602006009939D1 (de) | 2009-12-03 |
| IL187419A0 (en) | 2008-02-09 |
| EP1904471A1 (de) | 2008-04-02 |
| JP2009501158A (ja) | 2009-01-15 |
| AU2006269015A1 (en) | 2007-01-18 |
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